TAZ, also known as WWTR1, is a 14-3-3 binding protein with a PDZ binding motif. TAZ/WWTR1 is known to modulate mesenchymal stem cell differentiation
TAZ/WWTR1 was first cloned by Kanai et al. (2000). Kanai showed that TAZ RNA is most highly expressed in human kidney, followed by heart, placenta and lung. Expression was detected in all tissues tested except thymus and peripheral blood leukocytes. Northern blot analysis of mouse tissues showed transcripts expressed at highest levels in kidney, lung, liver, and heart and also in testis. Western blot analysis revealed expression of TAZ in several epithelial and fibroblast cell lines, but not in Jurkat T cells.
Mesenchymal stem cells are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, RUNX2 (OMIM reference 600211) and peroxisome proliferator-activated receptor-gamma (PPARG; OMIM reference 601487), drive mesenchymal stem cells to differentiate into either osteoblasts or adipocytes, respectively. Hong et al. (2005) found that TAZ/WWTR1 coactivates RUNX2-dependent gene transcription while repressing PPARG-dependent gene transcription.
By modulating Taz expression in model cell lines, mouse embryonic fibroblasts, and primary mesenchymal stem cells in culture and in zebrafish in vivo, Hong et al. (2005) observed alterations in osteogenic versus adipogenic potential. Hong et al. (2005) concluded that TAZ functions as a molecular rheostat that modulates mesenchymal stem cell differentiation.
Murakami (2005) show that TAZ acts as a potent TBX5 coactivator that physically associates with TBX5 and histone acetyltransferase (HAT) proteins and mediates TBX5-dependent gene activation. Murakami (2005) suggest that TAZ plays important roles in the control of TBX5-dependent genes during cardiac and limb development.
Hossain (2007) show that WWTR1 is critical for the integrity of renal cilia and its absence in mice leads to the development of renal cysts. Hossain (2007) concludes that Wwtrl may represent a candidate gene for polycystic kidney disease in humans.
In the Western world and the developed countries of Asia, breast carcinoma is the second leading cause of cancer-related death in women (Polyak, 2001). Breast cancer tops the cancer list for women in Singapore, with 700-800 new cases being diagnosed each year (Singapore Cancer Registry Report, 2000). In the USA, 180,000 women are diagnosed annually with new cases of breast cancer (Polyak, 2001). Despite better diagnosis and routine screening around a quarter of the cases will die from their disease.
Accordingly, there is a need for improved breast cancer detection and therapy.